Abstract
Background:Identifying host determinants associated with HIV reservoir size and timing of viral rebound after an analytic treatment interruption (ATI) is an important step in the search for an HIV functional cure. We performed a pooled analysis of 103 participants from 4 AIDS Clinical Trials Group ATI studies to identify the association between HLA class I alleles with HIV reservoir size and viral rebound timing.Methods:Total HIV DNA and cell-associated HIV RNA (CA-RNA) were quantified in pre-ATI peripheral blood mononuclear cell samples, and residual plasma viremia was measured using the single-copy assay. HLA class I typing was performed, and we generated an odds ratio (OR) of predicted HLA effect on HIV viremia control for each individual and compared this with time to viral rebound, and levels of HIV DNA and CA-RNA.Results:There was no significant association between the HLA ORs and levels of HIV DNA or CA-RNA, but carriage of protective HLA-B alleles (lower OR scores) was associated with delayed viral rebound (P = 0.02). Higher OR scores at the HLA-C locus were associated with longer duration of ART treatment (P = 0.02) and this trend was also seen with the combined OR score (P < 0.01). Individuals with protective HLA-B alleles had delayed viral rebound after treatment interruption that was not explained by differences in baseline reservoir size.Conclusions:The results indicate the vital role of cellular host immunity in preventing HIV rebound and the importance of taking into account the HLA status of study participants being evaluated in trials for an HIV cure.
Highlights
Antiretroviral therapy (ART) is effective at suppressing HIV replication in infected individuals, the virus persists in a stable pool of resting CD4+ T cells in the form of latent provirus that almost inevitably rebounds when treatment is stopped [1]
Eradication of HIV-1 disease necessitates the elimination of this latent reservoir, and identifying host determinants associated with latency and reservoir size in patients receiving antiretroviral therapy (ART) is an important step in the search for an intervention that provides sustained, long-term ART-free virological remission [2]
Using the results from that study, we examined the association between alleles at 3 human leukocyte antigen (HLA) class I loci (HLA-A, B, and C) and both reservoir size and viral dynamics after treatment interruption in participants of the AIDS Clinical Trials Group (ACTG) who underwent an analytic treatment interruption (ATI)
Summary
Antiretroviral therapy (ART) is effective at suppressing HIV replication in infected individuals, the virus persists in a stable pool of resting CD4+ T cells in the form of latent provirus that almost inevitably rebounds when treatment is stopped [1]. Using the results from that study, we examined the association between alleles at 3 HLA class I loci (HLA-A, B, and C) and both reservoir size and viral dynamics after treatment interruption in participants of the AIDS Clinical Trials Group (ACTG) who underwent an analytic treatment interruption (ATI). Identifying host genetic factors influencing the size of the infected cell population will provide insights into the mechanisms behind viral control after treatment interruption with implications for the efforts to induce ART-free HIV remission. Identifying host determinants associated with HIV reservoir size and timing of viral rebound after an analytic treatment interruption (ATI) is an important step in the search for an HIV functional cure. We performed a pooled analysis of 103 participants from 4 AIDS Clinical Trials Group ATI studies to identify the association between HLA class I alleles with HIV reservoir size and viral rebound timing
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
